Regulation of virulence gene expression in Staphylococcus aureus

摘要: The pathogenic bacterium Staphylococcus aureus has the ability to cause a wide variety of human diseases, ranging from superficial abscesses and wound infections deep systemic such as osteomyelitis, endocarditis septicaemia. disease been attributed large number toxins digesting enzymes well proteins at bacterial surface that bind various host molecules. These so-called virulence factors are accessory, supposed be synthesised in response specific needs during course infectious process. work described this thesis aims better understanding mechanisms regulate expression factors. Two interacting regulatory systems, agr (accessory gene regulator) sar (staphylococcal accessory regulator), involved regulation. locus, which encodes two-component signal transduction system responding cell density, controls least 25 different effector molecule is RNA molecule, named RNAIII. locus shown several staphylococcal genes by modulating activity agr, but also via agr-independent mechanisms. 14.7 kDa DNA binding protein, SarA. In animal models infection both sarA have affect virulence. How RNAIII function molecular level is, however, poorly understood. structure promoter studied detail showing SarA, regulates synthesis under certain growth conditions, binds multiple sites within region. It region 93 bp upstream transcription start point sufficient for agr-dependent regulation synthesis. coagulase negative species –S. epidermidis, S. simulans warneri– identified analysed. molecules staphylococci were able partially complement an deficient mutant. By construction hybrid it demonstrated highly conserved primary secondary structures 5 3 -half required genes, separate parts target genes. Several known regulated independent its effect on electrophoresis mobility shift experiments DNase footprinting, SarA found very similar way regions either activated or repressed sarA. does not appear recognise sequence motif rather AT-rich sequences. New potential regulators (RNAIII), hla (alpha-hemolysin), ssp (serine protease) spa (protein A) searched using linked magnetic beads. Of new candidate regulators, one protein with high degree similarity SarH1 (Sar Homologue 1) characterised part agr-sarA network controlling expression. computer searches unfinished genome databases four additional Sar homologues found, some may network.